肝细胞癌组织中DEPDC1B和KIF23的表达及其预后预测价值

Expression of DEPDC1B and KIF23 in hepatocellular carcinoma tissues and its clinical prognostic prediction value

目的探究肝细胞癌(HCC)组织中DEP结构域蛋白1B(DEPDC1B)和驱动蛋白家族成员23(KIF23)的表达及其预后预测价值。方法选择2018年3月至2019年3月湖南中医药高等专科学校附属第一医院诊治的126例HCC患者作为研究对象,收集其HCC组织、癌旁组织及临床资料。采用免疫组织化学法检测组织中DEPDC1B和KIF23的蛋白表达情况。分析癌症基因组图谱(TCGA)数据库中HCC组织和癌旁组织中DEPDC1B和KIF23的mRNA表达水平差异。分析HCC组织中DEPDC1B和KIF23的蛋白表达与患者临床病理特征的相关性。采用Kaplan-Meier曲线(Log-rank检验)分析DEPDC1B和KIF23的蛋白表达与患者预后的关系。采用单因素及多因素COX比例风险模型分析HCC患者预后的危险因素。结果TCGA数据分析结果显示,HCC组织中DEPDC1B和KIF23的mRNA相对表达量均显著高于癌旁正常肝组织(1.861±1.271比0.314±0.116,1.652±1.089比0.218±0.157,P均<0.0001)。HCC组织中DEPDC1B阳性表达主要位于细胞质和细胞膜,KIF23阳性表达主要位于细胞质和细胞核。HCC组织中DEPDC1B和KIF23的蛋白表达阳性率均显著高于癌旁组织[71.43%(90/126)比10.32%(13/126),χ^(2)=97.355,P=0.000;75.40%(95/126)比11.90%(15/126),χ^(2)=103.252;P=0.000]。HCC组织中DEPDC1B和KIF23的蛋白表达均与肿瘤分期、组织学分级及有无血管侵犯有关(P均<0.05)。HCC组织中DEPDC1B与KIF23的mRNA表达呈显著正相关(r=0.913,P=0.000),DEPDC1B与KIF23的蛋白表达亦呈显著正相关(Rs=0.811,P=0.000)。DEPDC1B阳性表达组的3年累积生存率显著低于DEPDC1B阴性表达组(χ^(2)=4.433,P=0.035)。KIF23阳性表达组的3年累积生存率显著低于KIF23阴性表达组(χ^(2)=6.125,P=0.013)。肿瘤分期Ⅱ~Ⅲ期、组织学分级Ⅲ级、血管侵犯、DEPDC1B阳性表达及KIF23阳性表达均是HCC患者预后的独立危险因素。结论HCC组织中DEPDC1B和KIF23的表达上调,两者均与肿瘤分期、组织学分级及有无血管侵犯有关,DEPDC1B、KIF23阳性表达均是HCC患者预后的独立危险因素。

Objective This paper intends to study the expression of DEP domain containing 1B(DEPDC1B)and kinesin family member 23(KIF23)in hepatocellular carcinoma(HCC)tissues,and to explore their clinical prognostic prediction value.Methods A hundred and twenty-six HCC patients diagnosed and treated at the First Affiliated Hospital of Hunan College of Traditional Chinese Medicine from March 2018 to March 2019 were selected as research subjects,and their HCC tissues,adjacent cancerous tissues,and clinical data were collected.The immunohistochemical method was used to detect the protein expression of DEPDC1B and KIF23 in tissues.The differential mRNA expression levels of DEPDC1B and KIF23 in HCC tissue and adjacent cancer tissues were analyzed in the Cancer Genome Atlas(TCGA)database.The correlation between the protein expression of DEPDC1B and KIF23 in HCC tissues and the clinical pathological characteristics of patients was analyzed.The Kaplan Meier curve(Log rank test)was used to analyze the relationship between the protein expression of DEPDC1B and KIF23 and patient prognosis.The univariate and multivariate COX proportional risk models were used to analyze the risk factors for prognosis in HCC patients.Results The TCGA data analysis results show that the relative mRNA expression levels of DEPDC1B and KIF23 in HCC tissues are significantly higher than those in normal liver tissues adjacent to cancer(1.861±1.271 versus 0.314±0.116,1.652±1.089 versus 0.218±0.157,and P<0.0001).The positive expression of DEPDC1B in HCC tissue is mainly located in the cytoplasm and cell membrane,while the positive expression of KIF23 is mainly located in the cytoplasm and nucleus.The positive expression rates of DEPDC1B and KIF23 proteins in HCC tissues are significantly higher than those in adjacent tissues(71.43%(90/126)versus 10.32%(13/126),χ^(2)=97.355,P=0.000;75.40%(95/126)versus 11.90%(15/126),χ^(2)=103.252;and P=0.000).The protein expression of DEPDC1B and KIF23 in HCC tissues are related to tumor staging,histological grading,and the presence or absence of vascular invasion(P<0.05).The mRNA expression of DEPDC1B and KIF23 in HCC tissues are significantly positively correlated(r=0.913 and P=0.000),and the protein expression of DEPDC1B and KIF23 are also significantly positively correlated(Rs=0.811 and P=0.000).The 3-year cumulative survival rate of the DEPDC1B positive expression group is significantly lower than that of the DEPDC1B negative expression group(χ^(2)=4.433 and P=0.035).The 3-year cumulative survival rate of the KIF23 positive expression group is significantly lower than that of the KIF23 negative expression group(χ^(2)=6.125 and P=0.013).Tumor stageⅡ-Ⅲ,histological gradeⅢ,vascular invasion,positive expression of DEPDC1B,and KIF23 are all independent risk factors for the prognosis of HCC patients.Conclusion The expression of DEPDC1B and KIF23 in HCC tissues are upregulated,and both are related to the tumor staging,histological grading,and presence or absence of vascular invasion,and the positive expression of DEPDC1B and KIF23 are independent risk factors for the prognosis of HCC patients.